Apparatus and methods for applying neural stimulation to a patient

ABSTRACT

Systems and methods for neural stimulation may include a stimulus unit; a first electrode assembly having a first set of contacts; and a second set of contacts. The stimulus unit can be an implantable pulse generator including a first terminal that can be biased at a first signal polarity and a second terminal that can be biased at a second signal polarity. The first electrode assembly includes a support member configured to be placed at the stimulation site, the first set of contacts carried by the support member, and a first lead configured to be attached to the first terminal of the implantable pulse generator for biasing the surface contacts at the first polarity. The second set of contacts is detached from the surface electrode assembly. The second set of contacts can be one or more conductive elements fixed to or forming portions of the implantable pulse generator, or a separate electrode array.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to pending U.S. Provisional ApplicationNo. 60/492,273, filed on Aug. 1, 2003, and incorporated herein in itsentirety by reference.

INCORPORATION OF RELATED APPLICATIONS

This application is related to U.S. patent application Ser. No.09/802,808 entitled “Methods and Apparatus for Effectuating a LastingChange in a Neural-Function of a Patient,” which claims the benefit ofU.S. Provisional Application 60/217,981, filed Jul. 31, 2000, both ofwhich are herein incorporated by reference. Additional applications areincorporated by reference in other portions of this application.

TECHNICAL FIELD

The present disclosure is related to systems and methods for applyingstimulation to a target neural population within a patient, for example,a surface site on the patient's cortex.

BACKGROUND

A wide variety of mental and physical processes are controlled orinfluenced by neural activity in particular regions of the brain. Theneural-functions in some areas of the brain (i.e., the sensory or motorcortices) are organized according to physical or cognitive functions,and various areas of the brain appear to have distinct functions in mostindividuals. In the majority of people, for example, the occipital lobesrelate to vision, the left interior frontal lobes relate to language,and the cerebral cortex appears to be involved with conscious awareness,memory, and intellect.

Many problems or abnormalities can be caused by damage, disease and/ordisorders in the brain. Effectively treating such abnormalities may bevery difficult. For example, a stroke is a common condition that damagesthe brain. Strokes are generally caused by emboli (e.g., obstruction ofa vessel), hemorrhages (e.g., rupture of a vessel), or thrombi (e.g.,clotting) in the vascular system of a specific region of the brain. Suchevents generally result in a loss or impairment of a neural function(e.g., neural functions related to facial muscles, limbs, speech, etc.).Stroke patients are typically treated using various forms of physicaltherapy to rehabilitate the loss of function of a limb or anotheraffected body part. Stroke patients may also be treated using physicaltherapy plus an adjunctive therapy such as amphetamine treatment. Formost patients, however, such treatments are minimally effective andlittle can be done to improve the function of an affected body partbeyond the recovery that occurs naturally without intervention.

Neurological problems or abnormalities are often related to electricaland/or chemical activity in the brain. Neural activity is governed byelectrical impulses or “action potentials” generated in neurons andpropagated along synaptically connected neurons. When a neuron is in aquiescent state, it is polarized negatively and exhibits a restingmembrane potential typically between −70 and −60 mV. Through chemicalconnections known as synapses, any given neuron receives excitatory andinhibitory input signals or stimuli from other neurons. A neuronintegrates the excitatory and inhibitory input signals it receives, andgenerates or fires a series of action potentials when the integrationexceeds a threshold potential. A neural firing threshold, for example,may be approximately−55 mV.

It follows that neural activity in the brain can be influenced byelectrical energy supplied from an external source such as a waveformgenerator. Various neural functions can be promoted or disrupted byapplying an electrical current to the cortex or other region of thebrain. As a result, researchers have attempted to treat physical damage,disease and disorders in the brain using electrical or magneticstimulation signals to control or affect brain functions.

Transcranial electrical stimulation is one such approach that involvesplacing an electrode on the exterior of the scalp and delivering anelectrical current to the brain through the scalp and skull. Anothertreatment approach, transcranial magnetic stimulation, involvesproducing a high-powered magnetic field adjacent to the exterior of thescalp over an area of the cortex. Yet another treatment approachinvolves direct electrical stimulation of neural tissue using implantedelectrodes.

The neural stimulation signals used by these approaches may comprise aseries of electrical or magnetic pulses directed toward affectingneurons within a target neural population. Stimulation signals may bedefined or described in accordance with stimulation signal parametersincluding pulse amplitude, pulse frequency, duty cycle, stimulationsignal duration, and/or other parameters. Electrical or magneticstimulation signals applied to a population of neurons can depolarizeneurons within the population toward their threshold potentials.Depending upon stimulation signal parameters, this depolarization cancause neurons to generate or fire action potentials. Neural stimulationthat elicits or induces action potentials in a functionally significantproportion of the neural population to which the stimulation is appliedis referred to as supra-threshold stimulation; neural stimulation thatfails to elicit action potentials in a functionally significantproportion of the neural population is defined as sub-thresholdstimulation. In general, supra-threshold stimulation of a neuralpopulation triggers or activates one or more functions associated withthe neural population, but sub-threshold stimulation by itself does nottrigger or activate such functions. Supra-threshold neural stimulationcan induce various types of measurable or monitorable responses in apatient. For example, supra-threshold stimulation applied to a patient'smotor cortex can induce muscle fiber contractions in an associated partof the body.

Although electrical or magnetic stimulation of neural tissue may bedirected toward producing an intended type of therapeutic,rehabilitative, or restorative neural activity, such stimulation mayresult in collateral neural activity. In particular, neural stimulationdelivered beyond a certain intensity, period of time, level, oramplitude can give rise to seizure activity and/or other types ofcollateral activity. It will be appreciated that certain types ofcollateral neural activity may be undesirable and/or inconvenient in aneural stimulation situation.

Another concern that arises in association with stimulating a surfacesite on a patient's cortex is conservation or minimization of appliedpower while operating a stimulation device. Various types of systemshave an implanted pulse generator (“IPG”) and an electrode assembly. Theelectrode assembly generally has a plurality of contacts that arecarried by a common support member, such that the contacts arepositionally fixed in close or generally close proximity relative toeach other. In operation, the IPG delivers an electrical waveform to theelectrode assembly, such that a first set of contacts provides a currentdelivery path and a second set of contacts provides a current returnpath. Thus, at any given time during waveform delivery, at least onecontact has a positive bias and at least one contact has a negativebias, resulting in the generation of a bipolar field at the surface ofthe cortex within the area of the stimulation site. The bipolar fieldhas a lower current density in the deeper layers of the cortex comparedto the current density at the surface layers, and the bipolar field runsgenerally parallel to the cranium of the patient in the deeper layers ofthe cortex. Systems that generate a bipolar field at the stimulationsite may require relatively high current levels to achieve an intendedor desired therapeutic effect. This may result in increased powerconsumption, and possibly increase the likelihood of inducing collateralneural activity.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side view of a system for applying electrical stimulation toa stimulation site on or proximate to the surface of the cortex of apatient in accordance with an embodiment of the invention.

FIG. 2 is a graph illustrating several parameters that may describe,define, or characterize a stimulation signal.

FIG. 3A is a front view of a system for applying electrical stimulationto a cortical stimulation site in accordance with FIG. 1A showing adifferent implementation of the system.

FIG. 3B is a cross-sectional view of a brain of a patient illustratingthe implementation of FIG. 3A in greater detail.

FIG. 3C is a schematic illustration of a combined electrode assemblythat may be used to apply or deliver unipolar stimulation to a patient.

FIG. 4 is a schematic illustration showing an exemplary electric fielddistribution generated by unipolar electrical stimulation using a systemfor applying electrical stimulation to a cortical stimulation site inaccordance with an embodiment of the invention.

FIG. 5 is a schematic illustration showing an exemplary electrical fielddistribution generated by bipolar electrical stimulation at a corticalstimulation site.

FIG. 6 is a side view of a system for applying electrical stimulation toa cortical stimulation site in accordance with another embodiment of theinvention.

FIG. 7 is a side view of a system for applying electrical stimulation toa cortical stimulation site in accordance with another embodiment of theinvention.

FIGS. 8A and 8B are an isometric view and a cross sectional view,respectively, of a system for applying electrical stimulation to a siteon or proximate to the cortex in accordance with another embodiment ofthe invention.

FIG. 8C is a cross sectional view of a system for applying electricalstimulation to a site on or proximate to the cortex according to anotherembodiment of the invention.

FIG. 9A is a schematic illustration of a system for applying electricalstimulation to a site on or proximate to the cortex in accordance withanother embodiment of the invention.

FIG. 9B is a schematic illustration of a system for applying electricalstimulation to a site on or proximate to the cortex in accordance withanother embodiment of the invention.

FIGS. 10–11 are flow charts illustrating methods for applying electricalstimulation to a stimulation site in accordance with embodiments of theinvention.

DETAILED DESCRIPTION

The present disclosure describes systems and methods for neuralstimulation that may enhance the efficacy and/or increase the efficiencyof neural stimulation procedures. The neural stimulation may comprise aset of stimulation signals applied or delivered to or through targetneural structures, target neural projections, and/or one or more targetneural populations associated with controlling, influencing, oraffecting one or more neurological functions under consideration. Theneural stimulation may be directed toward facilitating and/oreffectuating at least some degree of symptomatic relief and/orrestoration or development of functional abilities in patientsexperiencing neurologic dysfunction arising from neurological damage,neurologic disease, neurodegenerative conditions, neuropsychiatricdisorders, cognitive or learning disorders, and/or other conditions.Such neurologic dysfunction may correspond to Parkinson's Disease,essential tremor, Huntington's disease, stroke, traumatic brain injury,Cerebral Palsy, Multiple Sclerosis, a central pain syndrome, a memorydisorder, dementia, Alzheimer's disease, an affective disorder,depression, bipolar disorder, anxiety, obsessive/compulsive disorder,Post Traumatic Stress Disorder, an eating disorder, schizophrenia,Tourette's Syndrome, Attention Deficit Disorder, an addiction, autism,epilepsy, a sleep disorder, a hearing disorder (e.g., tinnitis orauditory hallucinations), a speech disorder (e.g., stuttering), and/orone or more other disorders, states, or conditions.

For example, relative to controlling, influencing, stabilizing,restoring, enhancing, or gaining a motor function, a target neuralpopulation may comprise one or more portions of a patient's motorcortex. A neural location at which or a neural region in whichstimulation signals are applied or delivered to or through a targetneural population may be defined as a stimulation site. Thus, for atarget neural population corresponding to the motor cortex, an exemplarystimulation site may comprise a location or region upon the patient'sdura mater.

As another example, relative to controlling, influencing, stabilizing,restoring, or enhancing an auditory function, a target neural populationmay correspond to one or more portions of a patient's auditory cortex. Astimulation site may comprise an epidural or subdural cortical regionthat may facilitate the application, delivery, and/or transfer ofstimulation signals to such a target neural population, for example, anepidural site adjacent or proximate to the Sylvian fissure. Theapplication of unipolar stimulation signals to such a stimulation sitein accordance with particular embodiments of the invention may increasea likelihood of affecting the target neural population in an intendedmanner.

A stimulation site may be identified in accordance with a variety oftechniques, including (1) identification of one or more anatomicallandmarks; (2) preoperatively (e.g., using Transcranial MagneticStimulation) and/or intraoperatively stimulating one or more brainlocations to identify or map particular neural regions that induce orevoke a given type of patient response (for example, a movement or asensation); (3) estimating a location at which the brain may recruitneurons to carry out a given type of neural activity that was previouslyperformed by a damaged portion of the brain; (4) an electrophysiologicsignal measurement and/or analysis procedure (e.g., acquisition and/oranalysis of EEG, EMG, MEG, coherence, partial coherence, and/or othersignals); and/or (5) a neural imaging procedure. In general, the numberand/or location of stimulation sites under consideration may depend uponthe nature, number, and/or extent of a patient's neurological conditionand/or functional deficits.

Several embodiments of such systems and methods apply or deliver aunipolar, monopolar, or isopolar stimulation signal that may provideenhanced efficacy or efficiency stimulation using a low current levelthat reduces power consumption and/or mitigates collateral effects.Various embodiments of the present invention may apply or deliver neuralstimulation at a subthreshold level or intensity, that is, at a levelthat raises or generally raises membrane potentials associated with atarget neural population while avoiding the generation of a sufficientor statistically significant number of action potentials capable oftriggering a neural function corresponding to the target neuralpopulation as a result of neural stimulation alone.

Stimulation systems and methods in accordance with the present inventionmay be used to treat various neurological conditions and/or facilitateparticular types of neurological or functional patient outcomes.Depending upon the nature of a particular condition, neural stimulationapplied or delivered in accordance with several embodiments of theinvention may affect neural firing likelihoods and/or influence,facilitate, and/or effectuate reorganization of interconnections orsynapses between neurons to (a) provide at least some degree offunctional recovery and/or functional gain; and/or (b) develop one ormore compensatory mechanisms to at least partially overcome a functionaldeficit or shortcoming. Such reorganization of neural interconnectionsmay be achieved, at least in part, by a change in the strength ofsynaptic connections through a process that corresponds to a mechanismcommonly known as Long-Term Potentiation (LTP). Neural stimulationapplied or delivered in accordance with certain embodiments of theinvention may alternatively or additionally affect particular neuralpopulations through a process that corresponds to a mechanism commonlyknown as Long-Term Depression (LTD). Neural stimulation delivered orapplied to one or more target neural populations either alone or inconjunction or association with one or more behavioral activities and/orother types of adjunctive or synergistic therapies (e.g., a drug orchemical substance therapy, a neurotrophic or growth factor therapy,and/or a cell implantation therapy) may facilitate, effectuate, orenhance therapeutic efficacy, for example, through neural plasticity andthe reorganization of synaptic interconnections between neurons.

A. Systems for Applying Electrical Stimulation

FIG. 1 is a side view of a system for applying electrical stimulation toa neural stimulation site or region according to an embodiment of theinvention. In various embodiments, the stimulation site may be upon,essentially upon, or proximate to the surface of the cortex of a patientP. The stimulation system may comprise a stimulus unit 120 and a patientinterface that includes a set of electrodes, electrode arrangementsand/or electrode assemblies 160 (hereinafter, “electrode assemblies”).In one embodiment, the set of electrode assemblies 160 includes a firstelectrode assembly 160 a and a second electrode assembly 160 b. Variousalternate embodiments may include additional electrode assemblies, whichmay be positioned or implanted at or proximate to a set of stimulationsites, or remote from one or more stimulation sites. Electrodeassemblies can stimulate different neural regions, e.g., regionscarrying out different neural functions and/or regions carrying outneural functions at different locations of the body, including differentextremities of the body.

Depending upon embodiment details, the system may also include a sensingunit 180 (shown schematically) configured to monitor one or more typesof patient responses, activities, and/or behaviors. The sensing unit 180may be further configured to communicate with the stimulus unit 120. Thesensing unit 180 may include, for example, electrodes 182 and/or otherdevices (e.g., an accelerometer or motion detector) configured to sensea patient's neural activity (e.g., an EEG signal), neuromuscularactivity (e.g., an EMG signal), behavioral activity (e.g., patientmotion), and/or other types of patient activity.

The stimulus unit 120 generates and outputs stimulation signals, and theset of electrode assemblies 160 facilitates application or delivery ofthe stimulation signals to the patient P. The stimulus unit 120 mayperform, direct, and/or facilitate neural stimulation procedures in amanner that enhances efficacy, mitigates a likelihood of inducingcollateral neural activity, and/or conserves power, as described indetail below.

The stimulus unit 120 may comprise a pulse generator that is implantedinto the patient P. In the embodiment shown in FIG. 1, the stimulus unit120 is an IPG that is implanted in a thoracic, subclavicular, orabdominal location. In other embodiments, the stimulus unit 120 can bean IPG implanted in the patient's skull or just under the patient'sscalp. For example, the stimulus unit 120 can be implanted above thepatient's neckline at a location in or near the patient's cranium.Examples stimulus units 120 suitable for implantation in a patient'scranium are set forth in U.S. patent application Ser. No. 09/802,808(previously incorporated by reference), as well as herein with referenceto FIGS. 8A through 9B.

The stimulus unit 120 may comprise a controller 130 and a pulse system140. The stimulus unit 120 may further comprise a power source, abattery, an energy storage device, and/or power conversion circuitry(not shown). The controller 130 may include a processor, a memory, and aprogrammable computer medium. The controller 130 may be implemented as acomputer or a microcontroller, and the programmable medium may comprisesoftware, instructions, and/or configuration information loaded into thememory and/or hardware that performs, directs, and/or facilitates neuralstimulation procedures in accordance with one or more methods of thepresent invention.

The pulse system 140 generates and outputs stimulation signals. FIG. 2is a graph illustrating several parameters that may describe, define, orcharacterize a stimulation signal. A stimulus start time t₀ may definean initial point at which a stimulation signal is applied to a targetneural population. In one embodiment, the stimulation signal may be asymmetric or asymmetric biphasic waveform comprising a set or series ofbiphasic pulses, and which may be defined, characterized, or describedby parameters including a pulse width t₁ for a first pulse phase; apulse width t₂ for a second pulse phase; and a pulse width t₃ for asingle biphasic pulse. The parameters can also include a stimulusrepetition rate 1/t₄ corresponding to a pulse repetition frequency; astimulus pulse duty cycle equal to t₃ divided by t₄; a stimulus bursttime t₅ that defines a number of pulses in a pulse train; and/or a pulsetrain repetition rate 1/t₆ that defines a stimulus burst frequency.Other parameters include a peak current intensity I₁ for the first pulsephase and a peak current intensity I₂ for the second pulse phase. Thoseskilled in the art will understand that pulse intensity or amplitude maydecay during one or both pulse phases, and a pulse may be acharge-balanced waveform. Those skilled in the art will furtherunderstand that in an alternate embodiment, pulses can be monophasic orpolyphasic.

In certain embodiments, the pulse system 140 may generate and/or outputstimulation signals in accordance with a theta burst pattern. Ingeneral, theta burst stimulation may comprise pulse bursts and/or pulsepackets separated by quiescent intervals, such that the number of pulsepackets per seconds corresponds or approximately corresponds to thetawave frequencies exhibited by the brain. In general, theta wavefrequencies may range from approximately 3 to 10 Hz, and moreparticularly in certain embodiments, 4 to 8 Hz.

In particular embodiments, the pulse system 140 may vary and/or modulatestimulation signals in one or more manners, for example, in accordancewith one or more mathematical operations and/or functions upon orcorresponding to particular stimulation signal parameters. Exemplarymanners of varying stimulation signals are described in detail in U.S.application Ser. No. 60/588,406, filed on Jul. 15, 2004, entitled“System and Method for Enhancing or Affecting Neural StimulationEfficiency and/or Efficacy,” incorporated herein by reference in itsentirety.

The pulse system 140 may apply or output stimulation signals to, across,or between a first terminal 142 a and a second terminal 142 b. Since astimulation signal may comprise a time-varying waveform, a relativepolarity of the stimulation signal, and hence that of the first andsecond terminals 142 a–b, may change or vary with time. With respect tooutputting one or more stimulation signals having phases that differ inpolarity, an anode may be defined as a terminal 142 a–b to which apositive polarity phase within an initial pulse is first applied. Forexample, for a stimulation signal comprising a series of biphasic pulseswhere each pulse includes a positive polarity phase followed by anegative polarity phase, where positive and negative may respectively bedefined relative to a zero potential level or a potential offset, ananode may be designated as the particular terminal 142 a–b that firstreceives a positive polarity phase following the stimulus start time t₀.A cathode may be defined as a terminal 142 a–b that provides electricalcontinuity for the stimulation signal delivered through the anodalterminal 142 a–b. The polarity of the cathode may thus be opposite tothat of the anode, or neutral. Depending upon embodiment details, acathode may be defined as a terminal 142 a–b to which a first negativepolarity or lower potential phase within an initial pulse is firstapplied. Those skilled in the art will recognize that the terms anodeand cathode could be defined in an opposite or different manner than asdefined above, yet such opposite or different definitions would beequivalent, essentially equivalent, or consistent from a mathematical orcircuit analysis perspective.

Depending upon embodiment details, (a) the first terminal 142 a may beconfigured as an anode, while the second terminal 142 b may beconfigured as a cathode; (b) the first terminal 142 a may be configuredas a cathode, while the second terminal 142 b may be configured as ananode; or (c) the first and second terminals 142 a–b may be selectivelyor programmably configured as an anode and a cathode, possibly in apredetermined, aperiodic, or pseudo-random time dependent manner. Suchanode/cathode selectivity may occur on a subseconds-based, aseconds-based, an hours-based, and/or another type of time domain,and/or may be facilitated by signal selection circuitry (e.g., amultiplexor or a switch matrix) and/or redundant output circuitry withinthe stimulus unit 120. In particular embodiments, stimulus periodsprovided by the stimulus unit 120 can have durations of 30 seconds orless, 10 seconds or less, 2–5 seconds, about one second, and/or lessthan one second. The stimulus periods can include but are not limited toalternating cathodal and anodal periods, alternating unipolar periods,alternating bipolar periods, and/or periods that alternate betweenunipolar and bipolar. The electrical potential of the stimulation signalcan also alternate between subthreshold levels and suprathresholdlevels.

The first electrode assembly 160 a may be positioned or implanted at astimulation site that is located upon, essentially upon, or proximate toa target neural population upon, within, or near the patient's cerebralcortex. The first electrode assembly 160 a may comprise a support member162 a and one or more contacts 164 a carried by the support member 162a. The support member 162 a may be configured for implantation at astimulation site upon or at least proximate to the surface of thepatient's cortex. The support member 162 a, for example, can be aflexible or rigid substrate that is implanted under the cranium S suchthat the contacts 164 a are positioned upon or adjacent to the duramater at the stimulation site. In other embodiments, the support member162 a can be a portion of a cranial screw or a housing that is implantedthrough the cranium S, in a manner identical or analogous to thatdescribed in U.S. patent application Ser. No. 10/418,796, which isincorporated herein by reference.

The first electrode assembly 160 a can have one or more contacts 164 aarranged or positioned in a desired configuration. For example, thefirst electrode assembly 160 a may include a single contact 164 a, or aplurality of contacts 164 a arranged as an array, grid, or otherpattern. In the embodiment shown in FIG. 1, the first electrode assembly160 a also includes a first lead or link 170 a that electrically couplessome or all of the contacts 164 a to the pulse system's first terminal142 a. The first electrode assembly 160 a may therefore be configured asan anode or a cathode, in accordance with the anodal or cathodalconfiguration of the first terminal 142 a of the pulse system 140.Contacts 164 a that are not coupled to the first terminal 142 a at aparticular time may electrically float. The first link 170 a may be awired link or a wireless link. The first electrode assembly 160 a cancomprise a cortical neural-stimulation device, such as any of thedevices described in U.S. patent application Ser. No. 09/802,808(previously incorporated herein by reference), and U.S. patentapplication Ser. No. 10/418,976, which is also incorporated by referenceherein.

The second electrode assembly 160 b can be similar to the firstelectrode assembly 160 a, or it can be a different type of electrodeassembly. The second electrode assembly 160 b may be positioned remotelyfrom the first electrode assembly 160 a. Since the second electrodeassembly 160 b provides electrical continuity with respect to the firstelectrode assembly 160 a, the second electrode assembly 160 b may bedefined to reside at a circuit completion site. In the embodiment shownin FIG. 1, the second electrode assembly 160 b comprises a separateelectrode array including a support base 162 b and one or more contacts164 b. In accordance with particular embodiment details, the supportbase 162 b can be configured for positioning at (a) a location or siteupon or proximate to the surface of the cortex spaced apart from thestimulation site where the first electrode assembly 160 a is located;(b) a deep brain location; or (c) another area in the body above orbelow the neck. The second electrode assembly 160 b can include a secondlink 170 b that couples one or more contacts 164 b (i.e., each contact164 b that is not electrically floating) to the second terminal 142 b ofthe pulse system 140. Thus, the second electrode assembly 160 b may beconfigured as an anode or a cathode, in accordance with the anodal orcathodal configuration of the pulse system's second terminal 142 b.

In the embodiment shown, the second electrode assembly 160 b, and moreparticularly the second electrode assembly's contacts 164 b, areseparate or otherwise detached from the first electrode assembly 160 a.Thus, the second electrode assembly's contacts 164 b are not attached tothe first electrode assembly 160 a, and the second electrode assembly'scontacts 164 b may be movable with respect to the contacts 164 a of thefirst electrode assembly 164 a before being implanted in the patient.The second electrode assembly 160 b may accordingly be configured to beattached to or implanted in the patient at a location spaced apart froma stimulation site on or proximate to the cortex of the patient whereelectrical stimulation is to be applied to facilitate and/or effectuatea given neurological or neurofunctional outcome, such as neuralplasticity or another type of neural reorganization corresponding to oneor more neural populations.

In the embodiment shown in FIG. 1, each contact 164 a of the firstelectrode assembly 160 a that is coupled to the pulse system's firstterminal 142 a (i.e., each non-floating contact 164 a) is biased inaccordance with a first signal polarity. Thus, the pulse system 140applies an identical polarity signal to each such contact 164 a at anygiven time. Correspondingly, each intentionally biased or non-floatingcontact 164 b of the second electrode assembly 160 b is biased inaccordance with a second signal polarity, where the second signalpolarity is opposite or complementary to the first signal polarity, orneutral, to facilitate electrical current flow between the first andsecond electrode assemblies 160 a–b.

Neural stimulation in which both an anode and a cathode are positioned,located, or situated within, essentially directly across, or proximateto a stimulation site may be defined as bipolar stimulation. Incontrast, neural stimulation in which one of an anode and a cathode ispositioned, located, or situated within or proximate to a stimulationsite, while a respective corresponding cathode or anode is positioned,located, or situated remote from the stimulation site to provideelectrical continuity may be defined as unipolar, monopolar, or isopolarstimulation. Thus, neural stimulation characterized by a biasingconfiguration in which an anode and a cathode are positioned, located,or situated in different neurofunctional areas or functionally distinctanatomical regions may be defined as unipolar stimulation. In a unipolarconfiguration, the pulse system 140 applies an identical polarity signalto each non-floating contact 162 a–b positioned upon or proximate to astimulation site. Unipolar stimulation may be defined as anodal unipolarstimulation when an anode is positioned upon or proximate to astimulation site or a target neural population; and as cathodal unipolarstimulation when a cathode is positioned upon or proximate to astimulation site or a target neural population.

In several embodiments, the second electrode assembly 160 b ispositioned apart or remote from the first electrode assembly 160 a toestablish an electric field that passes through deep layers of thecortex and/or other neural regions in a direction that is generallyperpendicular or oblique with respect to (a) the first electrodeassembly's contacts 164 a; (b) the surface of the cortex under the firstelectrode assembly 160 a; and/or (c) the cranium of the patient at orproximate to the stimulation site. The electric field, for example, issubstantially normal to the first electrode assembly 160 a in the deeplayers of the cortex and/or other neural layers beneath the stimulationsite.

FIGS. 3A and 3B illustrate a different implementation of a system forapplying electrical stimulation to a neural stimulation site accordingto an embodiment of the invention. In this embodiment, a first electrodeassembly 160 a may be implanted in the patient at a stimulation site atleast proximate to the surface of the cortex C (FIG. 3B) over targetneurons or a target neural population N (FIG. 3B). A second electrodeassembly 160 b may be positioned at a location in the patient that isspaced apart from the stimulation site, for example, at a location thatis above the patient's neck, to establish an electric field orientationor distribution that extends in a desired direction relative to thetarget neurons N. The second electrode assembly 160 b may additionallyor alternatively be positioned relative to other neural structures tominimize or mitigate collateral neural activity. The second electrodeassembly 160 b can be spaced apart from the patient's brain as shown inFIG. 3A, or the second electrode assembly 160 b can be positioned at adifferent location of the patient's brain as shown in FIG. 3B.

The stimulus unit 120 may provide an output at a first polarity to thenon-floating contacts 164 a of the first electrode assembly 160 a, andprovide an output at a second polarity to the non-floating contacts 164b of the second electrode assembly 160 b. The first electrode assembly'scontacts 164 a accordingly provide a unipolar, monopolar, or isopolarbias at the stimulation site upon or proximate to the patient's cortexC. The first polarity may be anodal or cathodal, and the second polaritymay respectively be cathodal or anodal (i.e., opposite to the firstpolarity or neutral). A unipolar signal applied to the first electrodeassembly's contacts 164 a may establish an electric field that extendsthrough deep layers of the cortex and/or other neural regions along avector V extending generally perpendicular to, or at least oblique withrespect to, the orientation of (a) the first electrode assembly 160 a;(b) the surface of the cortex C at or proximate to the stimulation site;and/or (c) the cranium of the patient adjacent to the stimulation site(FIG. 3A).

Certain systems and/or methods in accordance with the present inventionmay utilize or rely upon a single electrode assembly having a designthat is suitable for providing unipolar stimulation rather than relyingupon separate electrode assemblies. FIG. 3C is a schematic illustrationof a combined electrode assembly 260 capable of applying or deliveringunipolar stimulation to a patient. In one embodiment, the combinedelectrode assembly 260 includes a support member 262 having a localportion 263 a, a remote portion 263 b, and a separation portion 263 c.The local portion 263 a carries a first set of contacts 264 a, and theremote portion 263 b carries a second set of contacts 264 b. The supportmember 262 may be formed from one or more flexible or generally flexiblebiocompatible materials (e.g., plastic and/or silicone), and the firstand second sets of contacts 264 a–b may be formed from one or morebiocompatible conductive materials (e.g., Titanium and/or Platinum).Through appropriate couplings to a pulse system's first and secondterminals 142 a–b (for example, via a first and a second link 170 a–b),the first set of contacts 264 a may be configured as an anode or acathode, while the second set of contacts 264 b may respectively beconfigured as a cathode or an anode to facilitate unipolar stimulation.

The combined electrode assembly 260 may be implanted into a patient suchthat the local portion 263 a resides at, upon, or proximate to astimulation site, while the remote portion 263 b resides at a circuitcompletion site that is distant or remote from the stimulation site. Theseparation portion 263 c may have a length L that is sufficient toensure that in a typical patient, an electric field generated at or inthe vicinity of the local portion 263 a is substantially perpendicularto the patient's cranium, cortical surface, and/or targeted neuraltissues (which may include deep cortical layers or regions, as discussedbelow) beneath the stimulation site. In one embodiment, the value of Lmay be roughly an order of magnitude greater than the distance betweenthe stimulation site and a target neural population or neural regionthat is deepest or farthest from the stimulation site. For subduralstimulation, an exemplary value of L may be roughly an order ofmagnitude or more greater than approximately 2.5 to 3.0 mm; and forepidural stimulation, an exemplary value of L may be roughly an order ofmagnitude greater than approximately 4.0 to 6.0 mm.

The location, depth, and/or spatial boundaries of target neuralstructures and/or a target neural population may depend upon the natureof a neurological condition or disorder under consideration. The extentto which an electric field reaches, penetrates, and/or travels into orthrough target neural structures and/or a target neural population mayaffect neural stimulation efficiency and/or efficacy. An electric fieldgenerated by unipolar stimulation may reach or penetrate deeper neuralregions at a lower current level than an electric field generated bybipolar stimulation, as further described hereafter.

FIG. 4 is a schematic illustration showing an exemplary electric fielddistribution generated by unipolar stimulation using a system inaccordance with an embodiment of the invention. In FIG. 4, a firstcontact 164 a is positioned at a stimulation site corresponding to atarget neural population, while a second contact (not shown) ispositioned distant or remote from the first contact 164 a at a differentneurofunctional or anatomical region. The first contact 164 a may bebiased as an anode, for example, and the second contact may be biased asa cathode to establish an electrical potential gradient or differencethat facilitates the flow of electrical current (i.e., a net movement ofcharged particles or ions). A unipolar electric field distribution maybe represented as a plurality of field lines 300 that extend through,for example, targeted deep layers of the cortex C and possibly otherneural regions in a direction that is at least substantiallyperpendicular to (1) the surface of the cortex at or proximate to thestimulation site; and/or (2) the first electrode assembly's contacts 164a.

FIG. 5 is a schematic illustration showing an exemplary electric fielddistribution generated by bipolar stimulation, which may be selectivelyproduced in accordance with particular embodiments of the invention asfurther described below. In FIG. 5, a first contact 410 a and a secondcontact 410 b are configured to deliver bipolar stimulation to one ormore portions of a target neural population. The first and secondcontacts 410 a, 410 b are located proximate to each other, within orupon a stimulation site that corresponds to the spatial extent of thetarget neural population. In a bipolar configuration, contacts 410 a–bpositioned at and/or near the stimulation site are biased at differentpolarities. In FIG. 5, the first contact 410 a is biased as an anode,while a second contact 410 b is biased as a cathode. A bipolar electricfield distribution may be represented as a plurality of field lines 400having field components that are generally parallel to (1) the surfaceof the cortex at or proximate to the stimulation site; and/or (2) asupport member (not shown) configured to carry the first and secondcontacts 410 a–b.

In general, an electrical potential gradient or difference between ananode and a cathode configured to provide unipolar stimulation existsover a longer or greater distance than an electrical potential gradientbetween an anode and a cathode configured to provide bipolarstimulation. Thus, an anode to cathode electrical current pathwayassociated with unipolar stimulation will typically be longer than anelectrical current pathway associated with bipolar stimulation. Unipolarstimulation may therefore provide a greater degree of therapeuticefficacy than bipolar stimulation when stimulation of neural regions,structures, and/or projections that are deeper or more distant thanthose just beneath and/or in the near vicinity of the stimulation sitemay be of importance. Moreover, unipolar stimulation may deliver morecurrent to such deeper or more distant neural regions at a lower powerlevel than bipolar stimulation, which may result in greater stimulationefficiency and/or a reduced likelihood of inducing collateral neuralactivity. Enhanced stimulation efficiency may be important when treatingchronic, near-chronic, and/or longer-term conditions, for example,movement disorders or central pain syndrome.

In addition to or association with the foregoing, an electric fieldpolarity, orientation and/or distribution relative to particular typesof neurons, neural projections, neural structures, and/orneurofunctional regions may influence or affect neural stimulationefficiency and/or efficacy. The cortex C may be organized as a set of 6layers, where layer 1 maintains a boundary corresponding to the corticalsurface. Successive cortical layers exist or reside at increasing depthsrelative to the cortical surface. Thus, layer 6 corresponds to a deepestcortical layer. The thickness or extent of any given cortical layer, andthe type, number, and/or size of neurons, neural projections, and/orneural structures therein depends upon the cortical neurofunctionalregion under consideration.

Neurons convey input signals along their dendrites toward their cellbodies. Neurons in the cortex C include pyramidal cells 302 andinterneurons 304. In the motor cortex, the largest pyramidal cells 320have soma or cell bodies that reside in deep cortical layer 5. Pyramidalcells 302 have dendrites that project away from their cell bodies intooverlying or superficial cortical layers, toward the cortical surface ina manner that is approximately perpendicular or normal to the layerstructure of the cortex C. Interneurons 304 have cell bodies thatcommonly reside in cortical layers 2, 3, and 4, and include dendritesthat tend to project away from their cell bodies within the same layeror into an adjacent layer in a manner that is generally lateral orparallel with respect to the layer structure of the cortex C.

An optimal, near optimal, or desirable electric field orientation fortherapeutic neural stimulation may be based upon or determined by theorientation of one or more types of neurons, neural structures, and/orneural projections within or associated with a target neural populationN. For example, an electric field that is oriented generally parallel toa main or overall direction in which pyramidal cell dendrites project,that is, generally perpendicular or normal to the cortical layerstructure (or equivalently, generally perpendicular or normal to thesurface of the cortex C or the cranium), may preferentially influence orexert a more significant effect upon pyramidal cells 302 thaninterneurons 304, which include dendrites that generally project lateralto the cortical layer structure. In an analogous manner, an electricfield that is oriented generally parallel to a typical or overalldirection in which interneuron dendrites project, that is, generallyparallel or lateral to the cortical layer structure, may preferentiallyinfluence or exert a more significant effect upon interneurons 304 thanpyramidal cells 302.

In view of the foregoing, systems and/or methods in accordance withparticular embodiments of the invention may apply or deliver stimulationsignals having one or more polarities that may enhance a likelihood offacilitating or effectuating a desired neurological and/or functionaloutcome based upon the types of neurons, neural structures, and/orneural projections involved in subserving such an outcome. For example,specific embodiments of the invention may apply unipolar stimulation atone or more times to patients experiencing certain types of central painsyndrome. As another example, various embodiments of the invention mayapply unipolar stimulation, possibly in conjunction with a behavioraltherapy, to patients having functional deficits associated with stroke,traumatic brain injury, cerebral palsy, and/or other disorders (e.g.,tinnitus). In certain situations, unipolar stimulation may moreeffectively facilitate or effectuate neural disinhibition and/orneuroplastic change associated with a target neural population thanbipolar stimulation, thereby enhancing the extent to which such patientscan recover lost functional abilities and/or develop new abilities.

Unipolar stimulation may facilitate or effectuate enhanced recovery ordevelopment of functional abilities in patients experiencing particulartypes of neurologic dysfunction when compared to bipolar stimulation.For example, cathodal unipolar stimulation in conjunction or associationwith a behavioral therapy such as an Activity of Daily Living (ADL) mayfacilitate or effectuate a greater degree of functional developmentand/or recovery in a patient experiencing functional deficits associatedwith stroke, traumatic brain injury, and/or neurological damage thanbipolar stimulation either alone or in association or conjunction withsuch a behavioral therapy. Moreover, such enhanced recovery may occurusing lower current or average power levels than would be required forbipolar stimulation, thereby conserving power and/or reducing alikelihood of inducing collateral neural activity.

Certain systems and/or methods in accordance with the invention maydeliver unipolar stimulation during a unipolar stimulation period andbipolar stimulation during a bipolar stimulation period. For example,relative to facilitating or effectuating neuroplasticity, both pyramidalcells 302 and interneurons 304 may play a role in neural reorganization.Thus, a system and/or method may deliver unipolar stimulation to moreselectively influence or affect pyramidal cells 302 during a unipolarstimulation period, and deliver bipolar stimulation to more selectivelyinfluence or affect interneurons 304 during a bipolar stimulationperiod. One or more unipolar and/or bipolar stimulation periods may beidentical or different in duration, and may occur in a successive orgenerally successive manner, with or without one or more types ofintervening delays, interruptions, or cessations. Any given unipolarstimulation period, bipolar stimulation period, and/or interruptionperiod between unipolar and/or bipolar stimulation periods maycorrespond to a subseconds-based, a seconds-based, an hours-based,and/or another type of time domain. Depending upon embodiment details,alternation between unipolar and/or bipolar stimulation periods and/orintervals between such periods may temporally occur in a predetermined,aperiodic, or pseudo-random manner. Neural stimulation may be deliveredduring one or more unipolar and/or bipolar stimulation periods inconjunction or association with one or more adjunctive or synergistictherapies, for example, a behavioral therapy and/or a drug therapy. Anadjunctive therapy corresponding to a unipolar stimulation period may beidentical to or different from an adjunctive therapy corresponding to abipolar stimulation period.

In cortical regions associated with motor control, pyramidal cell axonsthat project into the spinal cord, brain stem, basal ganglia, and/orother areas may serve as cortical outputs involved in facilitating orcontrolling movement. In view of manners in which pyramidal celldendrites and axons project as described above, a given type of unipolarneural stimulation may elicit or generate a patient response or movementat a different (e.g., lower) current level or intensity than bipolarstimulation. Thus, unipolar stimulation may provide or induce anintended or desired effect at a lower current level than bipolarstimulation, thereby conserving power and/or reducing a likelihood ofinducing collateral activity. Similarly, unipolar stimulation mayfacilitate determination of a therapeutic current level using loweramplitude test stimulation signals than required by bipolar stimulation.In some embodiments, a therapeutic current level corresponding to agiven type of unipolar stimulation may be mapped to a therapeuticcurrent level that corresponds to a different type of unipolarstimulation and/or bipolar stimulation in accordance with a mappingfunction and/or empirical data.

In addition to the foregoing, certain types of neural cells may exhibitdifferent types of signal conductance properties based upon whether themotion of electrical charges or electrically charged particles (i.e.,ions) is toward or away from the axon hillock, the initial axonal regionproximate to the cell body through which dendritic inputs areintegrated. For instance, in pyramidal cells 302, intracellular ionsdiffusing toward the axon hillock experience a lower impedance thanintracellular ions diffusing toward the dendritic tree, thereby givingrise to an intracellular differential impedance (NeurophysiologicalTechniques: Applications to Neural Systems, Neuromethods 15, Eds. A. A.Boulton, G. B. Baker, and C. H. Vanderwolf). As a result, anodalunipolar stimulation may affect or influence a neural population, neuralstructures, and/or neural projections differently than cathodal unipolarstimulation.

Stimulation signal polarity characteristics may influence or affect anextent to which and/or a manner in which particular neural structuresexperience a potential difference and/or depolarization or polarizationrelative to each other, which may affect neural stimulation efficacyand/or efficiency. For example, due to the existence of a potentialgradient between a cathode and an anode, a relative dendrite to axonhillock or axon depolarization or hyperpolarization state may give riseto neural stimulation efficacy differences between cathodal unipolarstimulation and anodal unipolar stimulation.

During cathodal unipolar stimulation, a negative first pulse phaseapplied at a stimulation site may give rise to an intracellularconcentration of positive ions, thereby shifting the electrical state ofproximate dendrites toward a more depolarized state than, for example,axon hillocks corresponding to such dendrites.

In an analogous manner, during anodal unipolar stimulation, a positivefirst pulse phase applied at a stimulation site may give rise to anenhanced intracellular concentration of negative ions, thereby shiftingthe electrical state of such dendrites toward a more hyperpolarizedstate than axon hillocks corresponding to such dendrites.

A dendritic potential shift toward a more depolarized state and/or amore hyperpolarized state may affect dendritic signal processing and/orsignal generation and/or signal transfer mechanisms. Such a potentialshift may affect neural stimulation efficacy, for example, byinfluencing an extent to and/or manner in which postsynaptic dendritesreact or respond to and/or process presynaptic input.

In certain neural stimulation situations directed toward facilitatingand/or effectuating neural plasticity, cathodal unipolar stimulation mayincrease a likelihood that dendrites within a target neural populationrespond to and/or process neurofunctionally relevant synaptic input in amanner that enhances a likelihood of generating action potentials thatmay subserve the development and/or recovery of one or more functionalabilities. Neurofunctionally relevant synaptic input may arise from orcorrespond to an adjunctive or synergistic therapy, for example, abehavioral therapy. The aforementioned neural stimulation situations mayinclude, for example, neural stimulation directed toward rehabilitationof patients experiencing symptoms associated with neurological damage(e.g., arising from stroke or traumatic brain injury), neurodegenerativedisorders (e.g., Parkinson's disease, Alzheimer's disease),neuropsychiatric disorders (e.g., depression, OCD), and/or other typesof neurologic dysfunction.

In general, anodal or cathodal unipolar stimulation may be moreefficacious and/or efficient than cathodal or anodal unipolarstimulation, respectively, or bipolar stimulation in the context ofparticular neural stimulation situations, which may include, forexample, neural stimulation directed toward traumatic brain injury,cerebral palsy, movement disorders, central pain syndrome, tinnitus,neuropsychiatric disorders, auditory hallucinations, and/or otherconditions.

In particular neural stimulation situations, a likelihood of realizing agiven type of neurofunctional outcome may be enhanced through multipleanodal unipolar, cathodal unipolar, and/or bipolar stimulationprocedures, which may be applied in a simultaneous, alternating, and/orvarying manner. Such stimulation procedures may correspond to identical,generally identical, or different stimulation sites and/or stimulationparameters (e.g., pulse repetition frequency, first phase pulse width, apeak current and/or voltage amplitude or magnitude, theta burstcharacteristics, a waveform variation and/or modulation function, and/orother parameters) depending upon the nature of a patient's neurologicdysfunction, patient condition, and/or embodiment details. Moreover, anygiven stimulation procedure and/or an interval between stimulationprocedures may correspond to a subseconds-based, a seconds-based, anhours-based, and/or another type of time period or domain. In oneembodiment, before, during, and/or after one or more portions of acathodal stimulation procedure directed toward a first target neuralpopulation, an anodal unipolar stimulation procedure may be directedtoward a second target neural population. The first and second targetneural populations may reside in the same or different brainhemispheres.

FIG. 6 is a side view of a system for applying electrical stimulation toa surface site on the cortex in accordance with an embodiment of theinvention. In this embodiment, the system includes a stimulus unit 520and a patient interface including a first electrode assembly 560 a and asecond electrode assembly 560 b. The stimulus unit 520 can include acontroller 530 and a pulse system 540 similar to the controller 130 andpulse system 140 of the stimulation unit 120 described above withreference to FIG. 1. The stimulus unit 520 can also include a housing580 that is configured to be implanted or otherwise attached to thepatient.

The first electrode assembly 560 a can be similar to the first electrodeassembly 160 a described above with reference to FIG. 1. The firstelectrode assembly 560 a can accordingly include a support member 562 aconfigured to be implanted proximate to the cortex of the patient and atleast one surface contact 564 a. The surface contacts 564 a can becoupled to a first terminal 542 a of the stimulus unit 520 by a link570.

The second electrode assembly 560 b can be a separate item or elementattached to the stimulus unit 520, or the second electrode assembly 560b can be an integral component of the stimulus unit 520. The secondelectrode assembly 560 b, for example, can be a conductive portion ofthe housing 580 of the stimulus unit 520. In other embodiments, theentire housing 580 of the stimulus unit 520 can be a conductive materialthat defines the second electrode assembly 560 b, or a portion of thehousing 580 can be covered with an appropriate type of dielectric orinsulating material or be composed of such a material to limit theconductive surface area of the second electrode assembly 560 b to adesired shape or area. In still other embodiments, the second electrodeassembly 560 b is a separate set of contacts attached to the housing580. The second electrode assembly 560 b is coupled to a second terminal542 b of the pulse system 540.

The system shown in FIG. 6 operates by electrically biasing the surfacecontacts 564 a at an identical polarity, and biasing the secondelectrode assembly 560 b with an opposite or neutral polarity. Forexample, the system may be configured to deliver anodal unipolarstimulation to a stimulation site by biasing the surface contacts 564 aas an anode, and biasing the second electrode assembly 560 b as acathode. It will be appreciated that the surface contacts 564 a couldalternatively be biased as a cathode while the second electrode assembly560 b is biased as an anode. The system shown in FIG. 6 accordinglyprovides a unipolar signal at the stimulation site on or proximate tothe surface of the cortex of the patient.

Another aspect of the invention may involve configuring a neuralstimulation system to induce a desired electrical field and/or currentdensity at or proximate to a stimulation site as well as a remotecircuit completion site. In one embodiment, the aggregate surface areaof conductive surfaces that provide circuit completion or electricalcontinuity remote or generally remote from the stimulation site (e.g.,contacts 164 b carried by a second electrode assembly 160 b or 560 b, oran exposed conductive surface of a housing 580) is approximately200%–1500% of the aggregate surface area of conductive surfaces thatapply or deliver stimulation signals to one or more stimulation sites(e.g., contacts 164 a or 564 a carried by a first electrode assembly 160a or 560 a), and more specifically 250%–450%. The larger conductivesurface area corresponding to the circuit completion site reduces thecurrent density at the current completion site compared to thestimulation site; this is expected to reduce collateral neural activity,muscle activity, and/or patient sensation in the region of the circuitcompletion site.

FIG. 7 is a side view illustrating a system for applying electricalstimulation to a surface site on the cortex in accordance with anotherembodiment of the invention. In this embodiment, the system includes thestimulus unit 120, the second electrode assembly 160 b, and a surfaceelectrode assembly 660. The surface electrode assembly 660 can comprisean array including a support member 662 configured to be implanted atthe cortical stimulation site, a plurality of first surface contacts 664carried by one portion of the support member 662, and a plurality ofsecond surface contacts 665 carried by another section of the supportmember 662. The first surface contacts 664 are coupled to the first link170 a to electrically couple the first surface contacts 664 to the firstterminal 142 a of the stimulus unit 120. The second surface contacts 665can be coupled to the second link 170 b to electrically couple thesecond surface contacts 665 to the second terminal 142 b of the stimulusunit 120. The first surface contacts 664 can be biased as an anode, andthe second surface contacts 665 can be biased as a cathode, or viceversa. In an alternate embodiment, the second surface contacts 665 canbe connected to a separate link to be coupled to a third terminal of thestimulus unit 120. The second surface contacts 665 can accordingly bebiased independently of either the first surface contacts 664 or thesecond electrode assembly's contacts 164 b.

The embodiment of the system illustrated in FIG. 7 can provide acombination of unipolar and bipolar stimulation. For example, the firstsurface contacts 664 can be biased at a first polarity while the secondsurface contacts 665 or the return contacts 164 b are biased at a secondpolarity. In another embodiment, the second surface contacts 665 arecoupled to another terminal on the stimulus unit 120 so that the secondsurface contacts 665 can be biased separately from the return contacts164 b. This particular embodiment operates in a manner in which thefirst surface contacts 664 and the second electrode assembly's contacts164 b can be biased while not biasing the second surface contacts 665during a unipolar stimulation period, and then the first surfacecontacts 664 can be biased at the first polarity while the secondsurface contacts 665 are biased at the second polarity during a bipolarstimulation period. The stimulus unit 120 can alternate unipolarstimulation and bipolar stimulation periods according to a desiredsequence to provide a combination of unipolar and bipolar stimulation.

FIG. 8A is an isometric view and FIG. 8B is a cross sectional view of asystem for applying electrical stimulation to a surface site on orproximate to the cortex in accordance with another embodiment of theinvention. In one embodiment, the system comprises a support member 800that may carry a control unit 830 and a pulse system 840, plus a firstelectrode assembly 860 a and a second electrode assembly 860 b. Thesupport member 800 may include a housing 802 configured for implantationinto the skull 890, and an attachment element 804 configured forconnection to the skull 890 by fasteners, an adhesive, and/or an anchor.

The first electrode assembly 860 a may comprise a biasing element 862that carries a first set of electrical contacts 864 a. The biasingelement 862 may be formed using a soft, conformable, and/or compressiblebiocompatible material. In one embodiment, the first electrode assembly860 a is coupled to a first terminal 842 a of the pulse system 840. Thesecond electrode assembly 860 b may comprise one or more exposedconductive portions of the housing 802 and/or the attachment element804, and/or a second set of electrical contacts 864 b that are carriedby the housing 802 and/or the attachment element 804. The secondelectrode assembly 860 b may be coupled to a second terminal 842 b ofthe pulse system 840. Depending upon embodiment details, the pulsesystem's first and second terminals 842 a–b may be configured as ananode and a cathode, possibly in a selectable or programmable manner.Additionally, configuration or establishment of an anodal and a cathodalrelationship between the pulse system's first and second terminals 842a–b may occur in a predetermined, aperiodic, or pseudo-randomtime-varying manner.

The support member 800 may be implanted into or through a craniotomythat is above a stimulation site, such that one or more portions of thebiasing element 862 and/or the first set of contacts 864 a reside upon,essentially upon, or proximate to the stimulation site. Followingimplantation, the attachment element 804 may be covered by the patient'sscalp 892. The first electrode assembly 860 a may be biased inaccordance with a first polarity to apply or deliver unipolarstimulation to a target neural population, neural projections, and/orneural structures associated with the stimulation site. The secondelectrode assembly 860 b may be biased in accordance with a secondpolarity to provide electrical continuity for stimulation signalsdelivered by the first electrode assembly 860 a. In such aconfiguration, an electrical current pathway between the first andsecond electrode assemblies 842 a–b may include one or more portions ofthe patient's cortex, one or more neural regions below the cortex,vasculature, and/or portions of the patient's scalp. In order toeliminate, essentially eliminate, or minimize electrical current flowfrom the first electrode assembly 860 a to the second electrode assembly860 b along a current path that includes an interface between the skull890 and the edge of the housing 802 and/or the attachment element 804,one or more portions of the housing 802 and/or the attachment element804 may comprise or include an insulating material that forms anonconductive seal or barrier between the skull 890 and the housing 802and/or the attachment element 804.

FIG. 8C is a cross sectional view of a system for applying electricalstimulation to a surface site on or proximate to the cortex according toanother embodiment of the invention. Relative to FIGS. 8A and 8B, likereference numbers indicate like elements. In the embodiment shown inFIG. 8C, the first electrode assembly 860 a includes a first subset ofcontacts 865 coupled to the pulse system's first terminal 842 a.Additionally, the pulse system 840 includes a signal selection module880 capable of selectively coupling (1) a second subset of contacts 866to the first or second terminal 842 a–b of the pulse system 830; and/or(2) the second electrode assembly 860 b to the pulse system's secondterminal 842 b (in a manner that avoids simultaneous coupling of thesecond subset of contacts 866 to the first and second terminals 842a–b). The embodiment shown in FIG. 8C may thus be configured to provideunipolar stimulation by biasing the first subset of contacts 865 andpossibly the second subset of contacts 866 at a first polarity, andbiasing the second electrode assembly 842 b at a second polarity; orbipolar stimulation by biasing the first subset of contacts 865 at afirst polarity and the second subset of contacts 866 at a secondpolarity.

FIG. 9A is a schematic illustration of a system for applying electricalstimulation to a surface site on or proximate to the cortex inaccordance with another embodiment of the invention. Relative to FIGS.8A, 8B, and 8C, like reference numbers indicate like elements. In oneembodiment, the system comprises a support member 800 that carries acontroller 830, a pulse system 840, and a local electrode assembly 860.The system may further include at least one remote electrode assembly960. The support member 800 may include a housing 802 and an attachmentelement 804 as described above.

The local electrode assembly 860 may comprise a biasing element 862 thatcarries a first set of contacts 864. In one embodiment, the localelectrode assembly 860 is coupled to the pulse system's first terminal842 a. The remote electrode assembly 960 may comprise a support member962 that carries a second set of contacts 964, and may have a structureanalogous to one or more types of electrodes described in U.S. patentapplication Ser. No. 10/877,830, which is incorporated herein byreference. Alternatively, the remote electrode assembly 960 may comprisea cranial screw or peg type electrode as described in U.S. patentapplication Ser. No. 10/418,796 (previously incorporated herein byreference); or a depth, deep brain, or other type of electrode. Incertain embodiments, the remote electrode assembly 960 may provide anactive or aggregate conductive surface area that is greater than anactive or aggregate conductive surface area associated with the localelectrode assembly 860 in a manner analogous to that described above.The remote electrode assembly 960 may be coupled to the pulse system'ssecond terminal 842 b by a link 970. Depending upon embodiment details,the pulse system's first and second terminals 842 a–b may be configuredas an anode and a cathode, possibly in a selective, programmable,deterministic, and/or pseudo-random manner.

The support member 800 may be implanted into or through a craniotomythat is above a stimulation site in a manner analogous to that describedabove. The remote electrode assembly 960 may be implanted or positioneddistant or remote from the support member 800. The remote electrodeassembly 960, for example, may be positioned upon or beneath thepatient's skin at an anatomical location that is above or below thepatient's neck; or within the patient's cranium at a cortical,subcortical, or deep brain location that is distant, distinct, or remotefrom the local electrode assembly 860. The local electrode assembly 860may be biased in accordance with a first signal polarity, and the remoteelectrode assembly 960 may be biased in accordance with a second signalpolarity to provide unipolar stimulation.

FIG. 9B is a schematic illustration of a system for applying electricalstimulation to a surface site on or proximate to the cortex inaccordance with another embodiment of the invention. Relative to FIG.9A, like reference numbers indicate like elements. The embodiment shownin FIG. 9B includes a first and a second remote electrode assembly 960a–b, which may be identical, essentially identical, or different instructure. Any given remote electrode assembly 960 a–b may comprise anelectrode of a type indicated above. Depending upon embodiment details,the first and/or the second remote electrode assembly 960 a–b mayprovide an active or aggregate conductive surface area that is greaterthan an active or aggregate conductive surface area associated with thelocal electrode assembly 860 in a manner analogous to that describedabove. The first and second remote electrode assemblies 960 a–b arerespectively coupled to the pulse system's second terminal 842 b by afirst and a second link 970 a–b.

The embodiment shown in FIG. 9B may further include a signal selectionmodule 980 that facilitates selectable or programmable coupling of thefirst and/or second remote electrode assembly 960 a–b to the pulsesystem's second terminal 842 b. Depending upon embodiment details and/orthe nature of the patient's neurological condition, only one of thefirst and second remote electrode assemblies 960 a–b may be coupled tothe pulse system's second terminal 842 b at any given time; or the firstand second remote electrode assemblies 960 a–b may be coupled to thesecond terminal 842 b simultaneously.

In various embodiments, the support member 800 may be implanted at astimulation site in a manner analogous to that described above. Thefirst and second remote electrode assemblies 960 a–b may be respectivelypositioned or implanted at a first and a second anatomical location thatis distant, remote, or distinct from the stimulation site. The localelectrode assembly 860 may be biased in accordance with a first signalpolarity, while one or both of the remote electrode assemblies 960 a–bmay be biased in accordance with a second signal polarity at any giventime to provide unipolar stimulation.

The use of multiple remote electrode assemblies 960 a–b positioned atdifferent anatomical locations may provide multiple current pathwaysthrough which neural stimulation may affect or influence particulartarget cortical and/or subcortical neural populations, neuralstructures, and/or neural projections, possibly in an alternating ortime-dependent manner. For example, unipolar stimulation delivered orapplied along or with respect to a first current pathway may be directedtoward affecting neural activity in a first hemisphere of the brain,while unipolar stimulation applied with respect to a second currentpathway may be directed toward affecting neural activity in a secondhemisphere of the brain. Neural activity in each hemisphere mayinfluence the development, recovery, and/or retention of functionalabilities, possibly through neuroplastic mechanisms. In certainembodiments, one or more stimulation parameters such as stimulationsignal frequency, amplitude, and/or polarity may differ or vary inaccordance with a current pathway that is active or under considerationat any given time.

One or more embodiments described above may be modified to include orexclude elements or features described in association with otherembodiments, for example a signal selection module 880, 980.Additionally or alternatively, particular embodiments may includemultiple local electrode assemblies positioned at multiple stimulationsites, in conjunction with one or more remote electrode assembliespositioned distant from such stimulation sites to provide electricalcontinuity for unipolar stimulation.

B. Methods for Applying Electrical Stimulation

FIGS. 10–11 are flow charts illustrating various methods for applyingneural stimulation to a stimulation site in accordance with the presentinvention. FIG. 10, more specifically, illustrates a method 1000including a start procedure 1002, at least one unipolar stimulationprocedure 1004, and a decision procedure 1008. The unipolar stimulationprocedure 1004 includes establishing an electrical field by applying anelectrical signal having an identical first signal polarity to a firstset of contacts located at a stimulation site while applying a secondsignal polarity to a second set of contacts that is spaced apart orremote from the stimulation site. The unipolar stimulation procedure1004 may involve the application of anodal unipolar stimulation and/orcathodal unipolar stimulation to the patient, possibly in a manner thatincreases or enhances a likelihood or rate of patient functionalrecovery and/or development. Moreover, the unipolar stimulationprocedure 1004 may involve the application or delivery of stimulationsignals at a subthreshold and/or a suprathreshold level relative to thegeneration of a statistically and/or functionally significant number ofaction potentials in one or more target neural populations. The unipolarstimulation procedure 1004 may also involve the application or thetaburst stimulation signals during one or more time periods.

The unipolar stimulation procedure 1004 can be performed using any ofthe systems set forth above with respect to FIGS. 1–9B. The second setof contacts can be located apart from the stimulation site along avector that passes through deep layers of the cortex and/or other neuralregions in a direction that is oblique, and generally approximatelynormal, with respect to the first set of contacts at the stimulationsite. The unipolar stimulation procedure 1004, for example, may involveapplying a cathodal and/or an anodal signal to a set of active surfacecontacts 164 a to restore or at least partially recover speech,movement, and/or other functions that have been impaired by stroke orother brain damage.

An optional or alternative embodiment of the method 1000 can furtherinclude at least one bipolar stimulation procedure 1006 in which a firstset of contacts at a stimulation site are biased at a first signalpolarity, while a second set of contacts at a stimulation site arebiased at a second signal polarity. The bipolar stimulation procedure1006 may be performed in a manner identical or analogous to thatdescribed above, and may involve the delivery of stimulation signals ata subthreshold and/or a suprathreshold level. The bipolar stimulationprocedure 1006 may also involve the application of theta burststimulation signals during one or more time periods.

The decision procedure 1008 may decide whether the stimulation has beenof sufficient or adequate duration and/or effect. In particularembodiments, the decision procedure 1008 may involve monitoring ormeasuring patient progress and/or functional capabilities through one ormore standardized measures, tests, or tasks. Such standardized measuresmay include or be based upon, for example, a Fugl-Meyer Assessment ofSensorimotor Impairment; a National Institute of Health (NIH) StrokeScale; a Stroke Impact Scale (SIS); an ADL scale; a Quality of Life(QoL) scale; physical measures such as grip strength or finger tappingspeed; a neuropsychological testing battery; a walking, movement, and/ordexterity test; a behavioral test; a language test; a comprehensiontest; and/or other measures of patient functional ability. In certainembodiments, the decision procedure 1008 may alternatively oradditionally involve an electrophysiological signal acquisition and/oranalysis procedure, and/or a neural imaging procedure (e.g., MRI, fMRI,or PET). The decision procedure 1008 may direct the method 1000 to applyeither a unipolar stimulation procedure 1004 and/or a bipolarstimulation procedure 1006 depending upon the particular characteristicsof the therapy and/or the nature or extent of the patient'sneurofunctional condition. One or more stimulation sites and/orstimulation parameters (e.g., pulse repetition frequency, first phasepulse width, peak current and/or voltage amplitude, theta burstcharacteristics, a waveform variation and/or modulation function, and/orother parameters) corresponding to particular unipolar and/or bipolarstimulation procedures 1004, 1006 may be identical, generally identical,or different depending upon the nature of a patient's neurologicdysfunction, patient condition, and/or embodiment details. The method1000 may further include a termination procedure 1010 that is performedbased upon the outcome of the decision procedure 1008.

FIG. 11 illustrates a method 1100 in accordance with another embodimentof the invention. In one embodiment, the method 1100 includes a startprocedure 1102, a unipolar stimulation procedure 1104, and possibly afirst adjunctive or synergistic therapy procedure 1106. The unipolarstimulation procedure 1104 may involve the application or delivery ofanodal and/or cathodal unipolar stimulation signals to the patient,possibly in a manner that increases or enhances a likelihood and/or rateof patient functional recovery and/or development. Moreover, theunipolar stimulation procedure 1104 may involve subthreshold and/orsuprathreshold stimulation, and/or theta burst stimulation during one ormore time periods.

The unipolar stimulation procedure 1104 and the first adjunctive therapyprocedure 1106 can be performed concurrently or serially depending uponthe nature and/or extent of a patient's neurologic dysfunction, patientcondition, and/or embodiment details. The first adjunctive therapyprocedure 1106 may comprise a behavioral therapy procedure that caninclude a physical therapy, an activity of daily living, an intentionaluse of an affected body part, a speech therapy, a vision therapy, anauditory task or therapy (e.g., an auditory discrimination task), areading task, a memory task, a visualization, imagination, or thoughttask, and/or another type of task or therapy. A subthreshold unipolarstimulation procedure 1104 may be performed concurrent with a firstbehavioral therapy procedure 1106 to enhance or maximize a likelihoodgenerating action potentials that may subserve the development and/orrecovery of one or more functional abilities.

The method 1100 may additionally include a first decision procedure 1108that may decide whether the unipolar stimulation procedure 1104 and/orthe first adjunctive therapy procedure 1106 have been of sufficient oradequate duration and/or effect. The first decision procedure 1108 mayinvolve measurement or assessment of patient status, progress, and/orfunctional capabilities using one or more standardized measures, tests,or tasks; an electrophysiological signal acquisition and/or analysisprocedure; and/or a neural imaging procedure. If additional unipolarstimulation and/or adjunctive therapy is warranted, the method 1100 maycontinue, resume, or restart a unipolar stimulation procedure 1104and/or a first adjunctive therapy procedure 1106.

In certain embodiments, the method 1100 may further include a bipolarstimulation procedure 1110, and/or a second adjunctive or synergistictherapy procedure 1112. The bipolar stimulation procedure 1110 mayinvolve the application or delivery of stimulation signals at asubthreshold and/or suprathreshold level, and may possibly involve thetaburst stimulation at one or more times. The bipolar stimulationprocedure 1110 may be directed toward the same, essentially the same, ordifferent target neural structures, target neural projections, and/ortarget neural populations than the unipolar stimulation procedure 1104.Thus, the bipolar stimulation procedure 1110 may deliver or applystimulation signals to the same or a different stimulation site than theunipolar stimulation procedure 1104, either in the same and/or adifferent brain hemisphere. For example, both the unipolar and bipolarstimulation procedures 1104, 1110 may deliver stimulation signals toidentical or essentially identical portions of a patient's motor cortex;or the unipolar stimulation procedure 1104 may apply stimulation signalsto portions of the patient's motor cortex, while the bipolar stimulationprocedure 1110 may apply stimulation signals to portions of thepatient's premotor cortex or another region of the brain.

The second adjunctive therapy procedure 1112 may involve, for example, adrug therapy and/or a behavioral therapy that is identical oressentially identical to or different from a therapy associated with thefirst adjunctive therapy procedure 1106. The second adjunctive therapyprocedure 1112 may involve, for example, a visualization procedure suchas thinking about performing one or more types of motions and/or tasks,while the first adjunctive therapy procedure 1106 may involve attemptingto actually perform such motions and/or tasks.

Depending upon the nature and/or extent of a patient's neurologicdysfunction, patient condition, and/or embodiment details, the bipolarstimulation procedure 1110 and the second adjunctive therapy procedure1112 may be performed concurrently or serially, in a manner analogous tothat described above for the unipolar stimulation procedure 1104 and thefirst adjunctive therapy procedure 1106. Moreover, the bipolarstimulation procedure 1110 and/or the second adjunctive therapyprocedure 1112 may precede or follow the unipolar stimulation procedure1104 and/or the first adjunctive therapy procedure 1106 in either agenerally continuous or an interrupted manner.

The method 1100 may further include a second decision procedure 1114that may decide whether the bipolar stimulation procedure 1110 and/orthe second adjunctive therapy procedure 1112 have been of sufficient oradequate duration and/or effect. The second decision procedure 1114 mayinvolve measurement or assessment of patient status, progress, and/orfunctional capabilities using one or more standardized measures, tests,or tasks; an electrophysiological signal acquisition and/or analysisprocedure; and/or a neural imaging procedure. If additional bipolarstimulation and/or adjunctive therapy is warranted, the method 1100 maycontinue, resume, or restart a bipolar stimulation procedure 1110 and/ora second adjunctive therapy procedure 1112. Finally, the method 1100 mayinclude a termination procedure 1116 that may be performed based upon anoutcome of the first and/or second decision procedure 1108, 1116.

Depending upon embodiment details, a method 1100 may comprise a numberof anodal unipolar, cathodal unipolar, and/or bipolar stimulationprocedures 1104, 1110, where the number, duration of, and/or timebetween such procedures and/or the particular stimulation sites to whichsuch procedures are directed may be identical, essentially identical, ordifferent. Moreover, one or more stimulation signal parameters (e.g.,pulse repetition frequency, first phase pulse width, peak current and/orvoltage amplitude, theta burst characteristics, a waveform variationand/or modulation function, and/or other parameters) corresponding toparticular unipolar and/or bipolar stimulation procedures 1104, 1110 maybe identical, generally identical, or different depending upon thenature of a patient's neurologic dysfunction, patient condition, and/orembodiment details.

In certain embodiments, one or more procedures described herein may formportions of a limited duration treatment program, in a manner analogousto that described in U.S. application Ser. No. 10/606,202, incorporatedherein by reference. In accordance with various embodiments of thepresent invention, a limited duration treatment program may apply ordeliver unipolar stimulation, and possibly bipolar stimulation, to apatient for a limited period of time to facilitate or effectuatecomplete, essentially complete, significant, or partial rehabilitation,restoration, or functional healing of or recovery from a neurologicalcondition such as a neurological malfunction and/or a neurologicallybased deficit or disorder. Depending upon the extent or nature of thepatient's neurological condition and/or functional deficits, a limitedduration treatment program may last, for example, a number of weeks,months, or possibly one or more years.

From the foregoing, it will be appreciated that specific embodiments ofthe invention have been described herein for purposes of illustration,but that various modifications may be made without deviating from thespirit and scope of the invention. For example, aspects of the inventiondescribed in the context of particular embodiments can be combined oreliminated in other embodiments. Accordingly, the invention is notlimited except as by the appended claims.

1. A system for applying electrical stimulation to a patient's brain,comprising: an implantable housing; a pulse generator carried by theimplantable housing, the pulse generator having a first terminal and asecond terminal, the pulse generator being configured to deliver to atleast one of the first and second terminals a stimulation signal havinga plurality of stimulation periods with at least one of the stimulationperiods having a duration of about 30 seconds or less; at least onefirst electrode carried by the housing and operatively coupled to atleast one of the first and second terminals; and at least one secondelectrode carried by the housing and operatively coupled to at least oneof the first and second terminals, wherein the housing includes a firstportion and a second portion, and wherein the at least one firstelectrode is carried by the first portion of the housing so as to bepositioned at a cortical stimulation site of the patient located atleast approximately at or below an inner surface of the patient's skullwhen the housing is implanted, and wherein the at least one secondelectrode is carried by the second portion of the housing so as to bepositioned at least approximately at or above an outer surface of thepatient's skull and beneath the patient's scalp when the housing isimplanted.
 2. The system of claim 1 wherein the pulse generator isconfigured to deliver the stimulation signal with at least one of thestimulation periods having a duration of about 10 seconds or less. 3.The system of claim 1 wherein the pulse generator is configured todeliver the stimulation signal with at least one of the stimulationperiods having a duration of about one second or less.
 4. The system ofclaim 1 wherein the pulse generator is configured to deliver thestimulation signal with at least one of the stimulation periods having aduration of less than one second.